Chronic inflammation of blood vessels could help explain high childhood mortality in malaria regions

17 September 2013

Recurrent episodes of malaria cause chronic inflammation in
blood vessels that might predispose people to future infections and
may increase susceptibility to cardiovascular disease, a Wellcome
Trust study in Malawian children has found.

The findings could explain the indirect burden of malaria on
childhood deaths in areas where the disease is highly prevalent and
children experience multiple clinical episodes of malaria in a
year.

Malaria is caused when people become infected with a parasite
that starts by infecting the liver and then moves into the red
blood cells. The most deadly of the malaria parasites is Plasmodium
falciparum because of its ability to cause inflammation in blood
vessel walls, making them more sticky so that the infected red
blood cells can cling to the sides.

Being able to stick to the blood vessels in vital organs allows
the parasite to hide away from the immune system, a process called
sequestration. When it occurs in the brain it causes a more severe
form of the disease called cerebral malaria, which is associated
with seizures, coma and sometimes death.

It was thought that the changes in the blood vessel walls that
enable the infected red blood cells to stick would resolve quickly
once the cells had been cleared; however, the new findings show
that inflammation is still present up to one month later.

Researchers from the Malawi-Liverpool-Wellcome Clinical Research
Programme (MLW) at the University of Malawi College of Medicine in
Blantyre, Malawi, looked at 190 children with uncomplicated, mild
or cerebral malaria and healthy children of the same age. They
found that the changes were most pronounced in children with
cerebral malaria: the levels of one inflammatory molecule remained
22 times higher than in healthy controls one month after the
initial infection.

Dr Chris Moxon, a Wellcome Trust Clinical PhD Fellow and first
author of the study, explains: "These findings suggest that
children who live in areas of high malaria transmission have
persistently inflamed blood vessels, and that could have
significant effects on their long-term health.

"It could leave them more susceptible to repeated and more
severe infections with malaria, but also with other bacteria and
viruses, and chronic changes to the blood vessels like these could
be an important contributing factor to cardiovascular disease later
in life."

Professor Rob Heyderman, lead author and director of MLW, added:
"If follow-up studies in other populations confirm these findings,
we should consider whether existing anti-inflammatory drugs such as
statins may be able to limit these effects. Short courses of
statins could be targeted to children with severe and recurrent
disease to try and limit the severity of future infections, but
this would need to be evaluated in well-conducted clinical
trials."

Around 300 million clinical episodes of malaria are caused by
infection with the parasite P. falciparum each year. The disease is
transmitted by mosquitoes, and children living in areas where the
parasite is particularly prevalent may receive more than one
infective bite per day, resulting in repeated clinical episodes of
malaria over the course of the year.

Studies have shown that reducing malaria transmission in a
population such as this can reduce the number of childhood deaths
from any cause by up to 70 per cent, an effect that is much greater
than can be explained by reducing malaria alone. The findings from
this new study could offer some explanation for the unexplained
mortality in areas where malaria transmission is high.

Wellcome Trust researchers studying Malawian children
have found that recurrent malaria may cause chronic inflammation in
blood vessels. They say that this could, in turn, predispose people
to future infections and may increase susceptibility to
cardiovascular disease.

Malaria remains one of the most devastating diseases in
the developing world - according to the WHO, in 2010 there were an
estimated 219 million cases and 660,000 deaths. Its main victims
are children under the age of five in
Africa.

The study could explain the indirect burden of malaria on
childhood deaths in areas where the disease is highly
prevalent.

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